This proposal is the second revision of a competing continuation of a population-based case-control study designed to assess the association between myocardial infarction (MI) and the use of progestins in post- menopausal women at Group Health Cooperative (GHC). In this proposal, we present the final results on 502 MI cases and 1193 controls. Compared with users of neither estrogens nor progestins, the adjusted odds ratio (OR) for current use of estrogens alone was 0,69 with a 95% confidence interval (CI) of 0.47-1.02; and the adjusted OR for current use of combined therapy with estrogens and progestins was 0.68 (95% CI, 0.38-1.22). Based on the upper 95% CI, the data cannot exclude a 20-25% increase in the risk compared with never users. Our aims for this competing continuation are not only to make more precise some of the indeterminate findings related to current use, cumulative dose and duration of use but also to extend the assessment of the risk or benefit to incident strokes. All postmenopausal women aged 30- 79 yrs and enrolled in GHC will be eligible as cases if they present with an incident fatal or non-fatal MI or stroke during the 5-year period. A random sample of women from the GHC enrollment files will serve as controls, who will be frequency matched to cases on age and calendar year at a 3:1 ratio. Data collection efforts will include a review of the out- patient medical record. Analysis of data from the telephone interview suggested that after adjustment for the extensive information available from the medial record, there was little or no residual confounding from variables such as physical activity as assessed by interview; so we have decided to drop the interviews. Using computerized pharmacy data, we will assess the associations of MI and stroke with current and past use, dose and duration of estrogens alone and combined therapy. Data analysis will include the techniques of stratification and logistic regression. Continuing this project for 3 years will provide about 85% and 79% power for detecting an OR of 0.65 for MI and stroke, respectively, associated with combined therapy., The use of population based controls will enhance the validity of our findings -results which will provide evidence about the overall risk or benefit from the use of estrogens and progestins in post- menopausal women. Findings from the proposed study will complement those expected from the Women's Health Initiative in the year 2006.